This invention pertains to a method of and apparatus for forming cavities on solid formulations. More particularly, it pertains to a method of and apparatus for forming one or more cavities or holes on the surface of a solid formulation, such as a solid pharmaceutical dosage form, by employing a laser device.
Solid formulations are used for the delivery of active agents to an environment of use. Active agents generally include medicines, nutrients, food products, pesticides, herbicides, germicides, algaecides, chemical reagents, and others known to those of ordinary skill. When a solid formulation includes a core coated with a composition that is partially or completely insoluble in an intended environment of use, its coat(s) may include one or more perforations to permit release of the active agent from the core. Exemplary devices include osmotic devices, coated tablets, coated capsules, coated pills, coated lozenges, coated pellets, coated pastille and others. Some of these exemplary dosage forms employ osmotic pressure to control the release of the active agent contained in the core of the dosage form. These dosage forms may also include one or more layers, external to the core, comprising one or more materials that are subject to erosion or that slowly dissolve in the environment of use thereby gradually dispensing the active agent.
U.S. Pat. No. 4,088,864 to Theeuwes et al. and U.S. Pat. No. 4,063,064 to Saunders et al. disclose a high speed process for forming outlet passageways in the walls of osmotic devices for release of the contents of the osmotic device comprising: a) moving the pills in succession along a predetermined path at a predetermined velocity; b) tracking the moving pills seriatim at said velocity with a laser of a wavelength which is absorbable by said walls by oscillating the optical path of the laser back and forth over a predetermined section of the pill path at said velocity; c) firing the laser during said tracking; d) adjusting the laser beam dimension at said wall, the laser power and the firing duration being such that the laser beam is capable of piercing the wall; and e) forming, with the laser beam, an outlet passageway 4 to 2000 microns in diameter in the wall. These patents also disclose an apparatus for forming outlet passageways in the walls of osmotic devices for release of the contents of the osmotic device comprising: a) a support frame; b) a laser operating in a pulse mode; c) a laser-based optical pill-tracking mechanism; d) a rotary pill indexer; and e) an electrical power supply to supply and control power for the laser, the tracking mechanism, and the indexer.
U.S. Pat. No. 5,783,793 to Emerton et al. discloses a laser apparatus used to drill multiple holes on each side of a tablet sequentially without having to move the tablet. The apparatus includes mirrors and an acousto-optic deflector to reflect and deflect laser beam, respectively. The apparatus also includes an encoder coupled to the rotating shaft of a motor that rotates a tablet feeder. The encoder provides output signals that are used to regulate the timing of beam pulses so that the occurrence of beam pulses relative to tablet position, and hence the pattern generated, is synchronized.
U.S. Pat. No. 5,376,771 to Roy discloses a laser apparatus capable of simultaneously forming a plurality of holes on the semipermeable membrane of an osmotic device. The apparatus, marketed as the DIGIMARK(trademark) system, includes a linear array of individual laser tubes directed at a tablet surface. The different laser tubes can be pulsed independently of one another to created an array of circular or slotted apertures on the surface of the tablet.
U.S. Pat. Nos. 5,658,474 and 5,698,119 to Geerke et al. disclose a single beam laser apparatus for drilling holes into a single side of a tablet. The apparatus employs a laser beam diverting system, which is a series of mirrors, to determine the presence of a tablet in the tablet slot of a tablet feeder prior to entry of the tablet into the firing zone of the apparatus. If a tablet is detected in the tablet slot, the laser fires a pulse into the respective slot as it passes through the firing zone. The beam can be pulsed or continuous and more than one hole can be drilled into the same side of a tablet. The hole can be a continuous channel, a single hole or a series of overlapping holes. The hole can be shaped as a slot, polygon or circle.
U.S. Pat. No. 4,806,728 to Salzer et al. discloses a laser apparatus for perforating the surface of solid dosage forms. The apparatus creates a laser beam that has an adjustable spot size at different locations while maintaining a constant path length for the beam. This apparatus requires a beam focusing means, beam shaping means and a dichroic mirror for reflecting the beam. The beam is programmable and is used to produce a pattern on the surface of a solid dosage form.
U.S. Pat. No. 4,903,813 to Gajdos discloses a laser apparatus for applying markings or break-notches on tablet surfaces. The laser operation of the apparatus is synchronized with the operation of a tablet press. The apparatus includes a mirror that deflects the laser beam through a mask to create the marking or break-notch on the tablet surface. The laser is intensity modulated and it can be made telescopic or swiveling so that the laser can mark the top or side surface of the tablet.
U.S. Pat. Nos. 5,399,828 and 5,294,770 disclose a laser apparatus that fires multiple pulses at a single site of a tablet as it passes under a laser beam. The laser is synchronized with movement of a tablet conveyor. The apparatus includes a controller responsive to movement of the conveyor and to operation of laser. A laser pulse only occurs when a xe2x80x9claser-readyxe2x80x9d window in time coincides with a xe2x80x9ctablet-readyxe2x80x9d window in time. The apparatus can drill the top or bottom side of tablet. The laser beam is stationary and does not track the movement of the tablets. The apparatus can include a xe2x80x9csidexe2x80x9d detector to detect which side of tablet should be drilled. The apparatus can also include a pyroelectric detector off of the beam path to detect misfire of the beam and reject undrilled tablets. As with other systems, the apparatus can drill a series of holes on each side of the tablet. After passing through the firing zone all of the tablets enter a collection tube comprising an abort mechanism to separate drilled and undrilled tablets. The surfaces of the tablets are not examined and a determination that a tablet was not drilled is made by determining whether or not the laser fired a pulse at the tablet when the tablet passed through the firing zone. In order to synchronize the xe2x80x9claser-readyxe2x80x9d window with the xe2x80x9ctablet readyxe2x80x9d window, the apparatus includes a rotary encoder to provide periodic synchronization counts to the controller to synchronize the position of the moving tablets on the carrier means relative to the firing zone. Since the laser only fires when the xe2x80x9claser-readyxe2x80x9d and xe2x80x9ctablet readyxe2x80x9d windows are synchronized, a lead counter means responsive to the synchronization increment counts from the encoder is used to define the distance along the tablet path between the synchronization home count and the start of the treatment window corresponding to the leading edge of the treatment site on the moving tablet. Likewise, a window counter means responsive to the lead counter means and to the synchronization increment counts is used to define the distance along the tablet path between the start of the treatment window and the end of the treatment window corresponding to the trailing edge of the treatment site on the moving tablet. This system does not employ a sensor that actually detects the presence of a tablet in the slot of a conveyor, nor does it permit immediate return of undrilled tablets to the tablet reservoir. This system results in excess product loss due to the number of tablets that pass through the firing zone without being drilled. It also does not include process validation means or tablet inspection means subsequent to the firing zone to inspect the surface of the tablet shortly after drilling, validate performance of the apparatus and/or control operation of tablet diverting means.
While each of known systems includes its own advantages, each system is limited by one or more features that cause low rates of solids recovery. A need remains for a laser drilling system, optionally having an inspection system, that provides for high solids recovery and accurate drilling while at the same time providing ease of use and high efficiency.
The present laser drilling apparatus overcomes many of the disadvantages inherent in related prior art apparatuses by reducing the amount of solids lost due to malfunction or misfiring of the laser, by increasing process efficiency and improving system performance. Unlike the known systems, the present system also includes an optional process validation system. According to the embodiment of the invention, the laser apparatus is capable of: 1) immediately returning undrilled solids back to the solids reservoir; 2) detecting the presence of a solid in the solids chamber of an indexer by means other than deflection of the laser beam; 3) detecting the color of the surface of the solid prior to and, optionally, after drilling; 4) rejecting and, optionally, repositioning solids in the solids chamber of the indexer prior to drilling; 5) electronically and, optionally visually, inspecting the surface of the solid shortly after drilling to confirm the presence of a hole, the location of the hole, the number of holes and/or the shape of the hole; 6) electronically inspecting the surface of the solid to determine its color; 7) validating process performance by employing redundant but different sensing or detection means; 8) providing a summary of system performance for the laser drilling system; 9) synchronizing operation of multiple components of the laser apparatus; and/or 10) drilling tablets in a continuous, semicontinuous or batchwise operation.
One aspect of the invention provides a laser drilling system comprising:
a laser device that directs a pulsing laser beam at a firing zone;
a solids reservoir;
a continuous solids indexer comprising plural solids-receiving slots, wherein the indexer transports a solid from the reservoir through the firing zone to a delivery zone, and the laser device, in synchronization with the solids indexer, drills one or more holes or cavities in the surface of the solid; and
a first rejection means between the firing zone and the delivery zone for returning undrilled solids back to the solids reservoir prior to entering the delivery zone.
Another aspect of the invention provides a laser drilling system comprising:
a laser device that directs a pulsing laser beam at a firing zone;
a solids reservoir;
a continuous solids indexer comprising plural solids-receiving slots; wherein the indexer transports a solid from the solids reservoir through the firing zone to a delivery zone, and the laser device, in synchronization with the solids indexer, drills one or more holes or cavities in the surface of the solid;
an electronic inspection device in an analysis zone between the firing zone and the delivery zone; wherein the electronic inspection device determines the presence of a hole or cavity, the location of a hole or cavity, the number of holes or cavities and/or the shape of a hole or cavity drilled in the surface of the solid and/or determines the color of the solid; and
a solids-diverging means in the delivery zone and responsive to a direct or indirect signal from the inspection device.
Yet another aspect of the invention provides a laser drilling system comprising:
a laser device that directs a pulsing laser beam at a firing zone;
a solids reservoir;
a continuous solids indexer comprising plural solids-receiving slots; wherein the indexer transports a solid from the solids reservoir through a first detection zone and then the firing zone to a delivery zone, and the laser device, in synchronization with the solids indexer, drills one or more holes or cavities in the surface of the solid;
a solids detector in the first detection zone; wherein the solids detector detects the presence of a solid in a solids-receiving slot of the indexer by means other than the pulsing laser beam of the laser device; and
an optional color detector that detects the color of the surface of a solid in a solids-receiving slot.
Still another aspect of the invention provides a laser drilling system comprising:
a laser device that directs a pulsing laser beam at a firing zone;
a first solids reservoir comprising a fill detector;
a solids loading means adapted to conduct solids from a second solids reservoir into the first solids reservoir; wherein the solids loading means comprises a flow controller responsive to a signal from the fill detector;
a continuous solids indexer comprising plural solids-receiving slots; wherein the indexer transports a solid from the solids reservoir through the firing zone to a delivery zone, and the laser device, in synchronization with the solids indexer, drills one or more holes or cavities in the surface of the solid; and
a solids delivery zone.
Specific embodiments of the invention include combinations of the various embodiments described herein. Other embodiments include those wherein: 1) the apparatus further comprises solids-rejections means and, optionally, solids repositioning means between the solids reservoir and the firing zone; 2) the apparatus further comprises process validation means; 3) the apparatus comprises redundant detection means, wherein a first of the redundant detection means is disposed between the firing zone and the solids reservoir and the second of the redundant detection means is disposed between the firing zone and the solids delivery zone; 4) the apparatus further comprises a synchronizer that generates a synchronization signal used to synchronize operation of multiple components of the laser apparatus; 5) the apparatus is adapted for operation in a continuous, semicontinuous or batchwise manner; 6) the apparatus comprises a display for visually monitoring the operation of the inspection/validation device; 7) the inspection/validation system is computer and operator controlled; 8) the inspection/validation system employs learning, testing and inspection methods.
Other aspects of the invention provide a method of drilling a hole or cavity with a laser into a solid. The method comprises the steps of:
1) providing plural solids in a continuous solids indexer which obtains solids from a solids reservoir;
optionally first rejecting and/or repositioning an incorrectly positioned solid in the solids indexer, wherein a first rejected solid, if formed, is returned to the solids reservoir;
optionally detecting the presence and/or color of the solid in the solids indexer;
2) striking a solid with a laser pulse as the solids indexer passes it through a firing zone to form one or more holes, cavities or a combination thereof on the surface of the solid;
optionally second rejecting the solid if no hole or cavity is formed on the solid, wherein the second rejected solid, if present, is returned to the solids reservoir;
3) delivering the solid to a delivery zone;
optionally inspecting the solid to determine the presence of a hole or cavity, the location of a hole or cavity, the number of holes or cavities and/or the shape of a hole or cavity drilled in the surface of the solid and/or determine the color of the solid;
4) directing a correctly drilled, and optionally correctly colored, solid to an acceptance zone and directing a incorrectly drilled, optionally incorrectly colored, or optionally incorrectly drilled and incorrectly colored solid to a rejection zone.
Specific embodiments of the method include those wherein: 1) one or more of the above-described optional steps is performed; 2) the laser pulse comprises two or more micropulses; 3) additional solids are loaded into the solids reservoir in response to a direct or indirect signal generated by a fill detector; 4) the solids are loaded by gravity into the slots of the indexer; 5) the solids are inspected by capturing an electronic image of the solid and analyzing the captured image by comparing it to reference images; 6) the solids are first and second rejected by way of a stream or pulse of pressurized air; 7) the solids are directed to an acceptance zone or rejection zone by solids-diverging means; and/or 8) the slots of the indexer pass through the loading zone, firing zone, inspection zone, delivery zone and back to the loading zone.
Another aspect of the invention provides a control system for controlling operation of the laser drilling system. The control system employs a combination of software and hardware and controls operation of the various components of the system described above. The control system generally employs hardware for synchronizing and actuating operation of the detectors (sensors) and software for controlling the inspection, validation, and detection operations.
Other features, advantages and embodiments of the invention will become apparent to those skilled in the art by the following description, accompanying examples and appended claims.